In this project we propose to study the toxic effects of chlorinated and pyrethroid pesticides mainly on liver and nervous system. The main experimental animal to be used is rat. The compounds proposed for study are: DDT, chlordane, mirex, kepone, toxaphene, TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), PCB's allethrin, fenothrin, decamethrin, fenvalerate, and permethrin, etc. In the case of the liver effect, the major emphasis will be on the induction effects of these chemicals. The changes brought by long term administration in terms of alteration of cytochrome P-450 complex, protein synthesis, DNA and RNA synthesis, etc. will be studied. Efforts will be made to recognize group specific patterns of induction. In the case of TCDD, efforts will be made to study its inhibitory effects in the enzymes of the plasma membrane such as Na ion-K ion ATPase at the same time. The difference in the induction pattern between 3-methylcholanthrene and TCDD will be studied further. In the case of the nervous system, we plan to study the effects of these chemicals mainly on ATPase. We will critically examine their effects on Ca ion-ATPase so that the changes in the membrane Ca ions brought about by DDT and allethrin may be correlated to the excitation phenomena that these chemicals cause on the axons. In this particular case, nerve preparations from lobster and squid will be used since they are known to be rich with axonic membranes. Another important ATPase is Ca-Mg ATPase which is likely the Ca ion-sequestering apparatus of the presynaptic region. The inhibition of this enzyme could increase Ca ion concentration and thereby stimulate the transmitter release. We will investigate the relationship between the enzyme inhibition and the transmitter release by using various transmitter neurons.